苯肾上腺素对大鼠心肌纤维化的调节及其与转化生长因子-β1、果蝇母性DPP同源蛋白3及结缔组织生长因子信号通路的关系  

Effect of Phenylephrine on Myocardial Fibrosis Regulation With its Relevance to TGF-β/smads/CTGF Signal Pathway in Experimental Rats

作　　者：曹慧[1] 庞晓[1] 王硕[1] 唐燕[1] 

机构地区：[1]石河子大学医学院第一附属医院心内科,新疆维吾尔自治区石河子市832002

出　　处：《中国循环杂志》2016年第12期1205-1209,共5页Chinese Circulation Journal

基　　金：国家重点专科资助

摘　　要：目的:观察苯肾上腺素对压力超负荷介导的大鼠心肌纤维化(MF)的调节及其与转化生长因子-β1(TGF-β1)、果蝇母性DPP同源蛋白3(Smad3)及结缔组织生长因子(CTGF)信号通路的关系。方法:将雄性SD大鼠28只随机分为对照组、腹主动脉缩窄(AAC)组、AAC+苯肾上腺素组和AAC+哌唑嗪组,每组7只。通过心肌胶原形态学测定左心室组织胶原容积分数(CVF)观察大鼠MF的变化,应用免疫组化法检测各组大鼠左心室组织α-平滑肌肌动蛋白(α-SMA)、TGF-β1、Smad3及CTGF表达,用蛋白免疫印迹(Western blot)法测定左心室组织α-SMA表达。结果:(1)心肌胶原形态学显示:与对照组比,AAC组、AAC+苯肾上腺素组和AAC+哌唑嗪组的CVF均明显升高(P均<0.01);与AAC组比,AAC+苯肾上腺素组的CVF显著减少(P<0.01)。(2)免疫组化法显示:与对照组比,AAC组、AAC+苯肾上腺素组和AAC+哌唑嗪组的α-SMA、TGF-β1、Smad3及CTGF表达均上调(P均<0.01);与AAC组比,AAC+苯肾上腺素组的α-SMA、TGF-β1、Smad3及CTGF表达均降低(P均<0.01)。(3)Western blot法显示:与对照组比,AAC组、AAC+苯肾上腺素组和AAC+哌唑嗪组的α-SMA表达均上调(P均<0.05);与AAC组比,AAC+苯肾上腺素组的α-SMA表达降低(P<0.01)。结论:苯肾上腺素可以改善压力超负荷诱导的大鼠MF,该作用可能与抑制TGF-β1/Smads信号通路及下调CTGF有关。Objective： To observe the effect of phenylephrine（PE） on pressure overload induced myocardial fibrosis（MF） with its relevance to transforming growth factor-β1（TGF-β1）, drosophila mothers against decapentaplegic protein 3（smad3） and connective tissue growth factor（CTGF） signal pathway in experimental rats.Methods： A total of 28 male SD rats were randomly divided into 4 groups： Control group, AAC（abdominal aorta coarctation） group, AAC＋PE group and AAC＋prazosin group. n=7 in each group. Collagen volume fraction（CVF） of left ventricle was observed by myocardial collagen morphology, left ventricular myocardial tissue protein expressions of α-smooth muscle actin（α-SMA）, TGF-β1, smad3 and CTGF were measured by immunohistochemistry, protein expression of α-SMA was also examined by Western blot analysis.Results：（1） Myocardial collagen morphology presented that compared with Control group, AAC, AAC＋PE and AAC＋prazosin groups had increased CVF, all P〈0.01; compared with AAC group, AAC＋PE group had decreased CVF, P〈0.01.（2） Immunohistochemistry demonstrated that compared with Control group, AAC, AAC＋PE and AAC＋prazosin groups had up-regulated protein expressions of α-SMA, TGF-β1, smad3 and CTGF, all P〈0.01; compared with AAC group, AAC＋PE group had down-regulated protein expressions of α-SMA, TGF-β1, smad3 and CTGF, all P〈0.01.（3） Western blot analysis indicated that compared with Control group, AAC, AAC＋PE and AAC＋prazosin groups had the higher α-SMA expression, all P〈0.05; compared with AAC group, AAC＋PE group had the lower α-SMA expression, P〈0.01.Conclusion： Phenylephrine could improve pressure overload induced MF in experimental rats which might be related to TGF-β1/smads signal pathway inhibition and CTGF down-regulation.

关 键 词：苯肾上腺素 心肌纤维化 转化生长因子-Β1 

分 类 号：R54[医药卫生—心血管疾病]